Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature.

<h4>Background</h4>Heart failure (HF) is characterized by complex molecular alterations, and recent studies suggest a potential role for sepsis-related genes in cardiovascular dysfunction. This study aimed to develop a predictive model for HF based on sepsis-related gene signatures.<h...

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Main Authors: Yiping Lang, Tianyu Liang, Fei Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0326212
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author Yiping Lang
Tianyu Liang
Fei Li
author_facet Yiping Lang
Tianyu Liang
Fei Li
author_sort Yiping Lang
collection DOAJ
description <h4>Background</h4>Heart failure (HF) is characterized by complex molecular alterations, and recent studies suggest a potential role for sepsis-related genes in cardiovascular dysfunction. This study aimed to develop a predictive model for HF based on sepsis-related gene signatures.<h4>Methods</h4>Three sepsis-related datasets (GSE65682, GSE54514, and GSE95233) were analyzed to identify differentially expressed genes (DEGs) following batch effect correction using the ComBat algorithm. With the use of elastic net regularization and the glmnet package in R, Lasso Cox regression was employed to screen out gene signatures. A predictive model was developed based on the expression of each gene signature and the co-efficient values. In addition, the predictive model was validated on independent HF datasets (GSE57345, GSE141910, and GSE5406). Model performance was assessed through receiver operating characteristic (ROC) analysis and AUC values of each gene signature, and immune infiltration was evaluated using CIBERSORT, IPS, and xCell. Sepsis models of C57BL/6 mice were established by cecal ligation and puncture (CLP).<h4>Results</h4>We identified 340 up-regulated and 333 down-regulated sepsis-related genes. The predictive model, incorporating six key genes, demonstrated superior performance compared to individual genes across both training and validation datasets with the AUC value of the risk score above 0.9, significantly higher than that of a single gene. Immune infiltration profiles differed significantly between HF patients and controls, with more pronounced alterations observed at higher risk score levels. Finally, the expression of six key genes in sepsis models was confirmed to be consistent with our prediction.<h4>Conclusion</h4>The model constructed through sepsis-related characteristic genes provides a highly advantageous method for predicting HF, and the characteristic genes we have screened may be potential biomarkers for predicting HF. This model has potential application value in early diagnosis and risk stratification, which can help improve the clinical management of heart failure and provide new ideas for preventing HF.
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spelling doaj-art-894d4069eadc474c9023b0bbff687caf2025-08-20T02:37:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01206e032621210.1371/journal.pone.0326212Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature.Yiping LangTianyu LiangFei Li<h4>Background</h4>Heart failure (HF) is characterized by complex molecular alterations, and recent studies suggest a potential role for sepsis-related genes in cardiovascular dysfunction. This study aimed to develop a predictive model for HF based on sepsis-related gene signatures.<h4>Methods</h4>Three sepsis-related datasets (GSE65682, GSE54514, and GSE95233) were analyzed to identify differentially expressed genes (DEGs) following batch effect correction using the ComBat algorithm. With the use of elastic net regularization and the glmnet package in R, Lasso Cox regression was employed to screen out gene signatures. A predictive model was developed based on the expression of each gene signature and the co-efficient values. In addition, the predictive model was validated on independent HF datasets (GSE57345, GSE141910, and GSE5406). Model performance was assessed through receiver operating characteristic (ROC) analysis and AUC values of each gene signature, and immune infiltration was evaluated using CIBERSORT, IPS, and xCell. Sepsis models of C57BL/6 mice were established by cecal ligation and puncture (CLP).<h4>Results</h4>We identified 340 up-regulated and 333 down-regulated sepsis-related genes. The predictive model, incorporating six key genes, demonstrated superior performance compared to individual genes across both training and validation datasets with the AUC value of the risk score above 0.9, significantly higher than that of a single gene. Immune infiltration profiles differed significantly between HF patients and controls, with more pronounced alterations observed at higher risk score levels. Finally, the expression of six key genes in sepsis models was confirmed to be consistent with our prediction.<h4>Conclusion</h4>The model constructed through sepsis-related characteristic genes provides a highly advantageous method for predicting HF, and the characteristic genes we have screened may be potential biomarkers for predicting HF. This model has potential application value in early diagnosis and risk stratification, which can help improve the clinical management of heart failure and provide new ideas for preventing HF.https://doi.org/10.1371/journal.pone.0326212
spellingShingle Yiping Lang
Tianyu Liang
Fei Li
Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature.
PLoS ONE
title Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature.
title_full Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature.
title_fullStr Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature.
title_full_unstemmed Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature.
title_short Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature.
title_sort integrated multi omics analysis and predictive modeling of heart failure using sepsis related gene signature
url https://doi.org/10.1371/journal.pone.0326212
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